In this paper,we introduce the censored composite conditional quantile coefficient(cC-CQC)to rank the relative importance of each predictor in high-dimensional censored regression.The cCCQC takes advantage of all usef...In this paper,we introduce the censored composite conditional quantile coefficient(cC-CQC)to rank the relative importance of each predictor in high-dimensional censored regression.The cCCQC takes advantage of all useful information across quantiles and can detect nonlinear effects including interactions and heterogeneity,effectively.Furthermore,the proposed screening method based on cCCQC is robust to the existence of outliers and enjoys the sure screening property.Simulation results demonstrate that the proposed method performs competitively on survival datasets of high-dimensional predictors,particularly when the variables are highly correlated.展开更多
Objective:To explore the relationship between cancer awareness and the survival of the patients with non-small cell lung carcinoma(NSCLC).Methods:A total of 865 NSCLC patients were screened for the risk factors,includ...Objective:To explore the relationship between cancer awareness and the survival of the patients with non-small cell lung carcinoma(NSCLC).Methods:A total of 865 NSCLC patients were screened for the risk factors,including age,gender,address,tumor/lymph nodes/metastasis(TNM)stage,and cancer awareness.Survival of the patients was calculated by Kaplan-Meier method and Cox regression analysis.Results:After an average observation time of 304 d(ranging from 0 to 4718 d),62 of the 394 patients in the cancer awareness group survived,whereas 26 of the 471 patients in the cancer concealment group survived.Cancer-specific and all-cause survival was poorer in the cancer concealment group(P<0.001 for each,log-rank test).Cox multivariate regression analysis showed that cancer concealment displayed significantly lower cancer-specific survival[hazard ratio(HR)=1.534,95%con fi dence interval(CI)1.320 to 1.784,P<0.001]and all-cause survival(HR=1.558,95%CI 1.346 to 1.803,P<0.001).Conclusion:Cancer concealment is associated with a poor survival of NSCLC patients,which may prohibit the patients from obtaining the real“right to survival”.展开更多
Probiotics which can provide potential health benefits for consumers and prevent disease, is the most important research field for functional food in the future. It is the key point that how much the count of bacteria...Probiotics which can provide potential health benefits for consumers and prevent disease, is the most important research field for functional food in the future. It is the key point that how much the count of bacteria and how long it can preserve. Freeze-drying skill is one of the best preservation methods, but it＇s defect that damage to biological systems can be attributed to changes in the physical state of membrane lipids or/and changes in the structure of sensitive proteins and the decreased survival rate. This work used pretreatment methods-cold shock and hot shock to reduce the damage to bacteria during freeze-drying. Using unpretreated samples as control, aspects of cold shock or heat shock. The response of Enterococcous faecalis A31 was investigated during lag phase, the middle of exponential growth phase and the terminal of exponential growth phase. The results suggested that when cold shock, the shock protein concentration produced by treated sample within 2 h during the middle of exponential growth phase was higher than 4, 8, 24 h, The concentration of shock protein produced by treated sample at 10 ℃ was higher than 20℃, The concentration of sample protein at the middle of exponential growth phase was higher than that at the terminal of exponential growth phase. After one-month storage, the survival rate at 10℃ was better than 20 ℃ and 4 ℃comparatively. The survival rate at （6 h） 4 ℃/24 h （lag period） was higher than （10 h） 4 ℃/24 h （the middle of exponential growth phase）, and the effect of 10℃/8 h shock treatments was best during the middle of exponential growth phase, when hot shock, The concentration of heat shock proteins produced was not obvious, and survival rate was higher at 45 ℃, 30 min than at 45 ℃, 60 min.展开更多
Heliostats are sensitive to the wind load, thus as a key indicator, the study on the static and dynamic stability bearing capacity for heliostats is very important. In this work, a numerical wind tunnel was establishe...Heliostats are sensitive to the wind load, thus as a key indicator, the study on the static and dynamic stability bearing capacity for heliostats is very important. In this work, a numerical wind tunnel was established to calculate the wind load coefficients in various survival stow positions. In order to explore the best survival stow position for the heliostat under the strong wind, eigenvalue buckling analysis method was introduced to predict the critical wind load theoretically. Considering the impact of the nonlinearity and initial geometrical imperfection, the nonlinear post-buckling behaviors of the heliostat were investigated by load-displacement curves in the full equilibrium process. Eventually, combining B-R criterion with equivalent displacement principle the dynamic critical wind speed and load amplitude coefficient were evaluated. The results show that the determination for the best survival stow position is too hasty just by the wind load coefficients. The geometric nonlinearity has a great effect on the stability bearing capacity of the heliostat, while the effects of the material nonlinearity and initial geometrical imperfection are relatively small. And the heliostat is insensitive to the initial geometrical imperfection. In addition, the heliostat has the highest safety factor for wind-resistant performance in the stow position of 90-90 which can be taken as the best survival stow position. In this case, the extreme survival wind speeds for the static and dynamic stability are 150 m/s and 36 m/s, respectively.展开更多
Objective Diabetic patients pose a greater challenge in managing chronic wound healing,leading to a higher amputation risk compared to non-diabetic patients.Due to their paracrine function by secreting various cytokin...Objective Diabetic patients pose a greater challenge in managing chronic wound healing,leading to a higher amputation risk compared to non-diabetic patients.Due to their paracrine function by secreting various cytokines and angiogenic factors,mesenchymal stem cells(MSCs)have been acknowledged to be a potential agent in modulating wound healing process.However,post-transplanted MSCs are vulnerable to death,indicating poor survival and migration ability in the wound site of the host,especially under hyperglycemia.As hyperglycemia induces reactive oxygen species(ROS)generation and cellular apoptosis,improvement of MSCs survival and migration potentials under hyperglycemia could contribute to a more efficient MSCs-based wound healing therapy.Salidroside(Sa),a small-molecule drug derived from Rhodiola plant,has been proved to enhance the paracrine function of skeletal muscle cells,as well as their migration even under hypoxichyperglycemia.Herein,we investigated whether Sa could improve the survival and migration potentials of MSCs,subsequently enhance the wound healing process under hyperglycemia.Methods MSCs were cultured under three conditions:low glucose,high glucose,and high glucose+Sa.qPCR analysis and western blotting were done to examine the mRNA and protein expression level of several factors which are important in upregulating the wound healing process.MTT colorimetric assay,intracellular ROS detection,and flow cytometry assay were employed to examine the effect of Sa in MSCs survival.Transwell chamber assay,scratch assay,and phalloidin staining were done to elucidate the role of Sa in regulating MSCs migration potential.For in vivo experiment,diabetic wound healing mice model was generated to elucidate the effect of Sa-pretreated MSCs transplantation in wound closure rate,as well as re-epithelization status,observed with hematoxylin and eosin staining.The diabetic wound healing mice model were divided into three groups:1)mice injected with PBS,2)mice transplanted with PBS-pretreated MSCs,and 3)mice transplanted with Sa-pretreated MSCs.Results(1)Hyperglycemic condition induced the generation of ROS and suppressed total cell number of MSCs,while Sa treatment into MSCs restored these hyperglycemia-induced alterations.In line with this,total apoptotic cells were also suppressed by treating MSCs with Sa.The expression level of cell survival factor,heme-oxygenase 1(HO-1),was enhanced in Sa-pretreated MSCs.Further treatment of HO-1 inhibitor into Sa-pretreated MSCs nullified the ROS level and total apoptotic cells,indica-ting the importance of HO-1 in mediating the Sa-induced survival of MSCs under hyperglycemia.(2)Transwell chamber and scratch assay results showed that Sa-pretreated MSCs have a higher migration potential under hyperglycemia,supported by higher F-actin polymerization fractal dimension.Fibroblast growth factor 2(FGF2)and hepatocyte growth factor(HGF)expression level,which are essential factors for cell migration,were also improved in Sa-pretreated MSCs under hyperglycemia.(3)In diabetic wound healing mice model,transplantation of Sa-pretreated MSCs resulted in significantly improved wound closure rate and re-epithelization.The protein levels of HO-1,FGF2,and HGF were also enhanced in the tissues obtained from the wound site of diabetic wound healing mice model which were transplanted with Sa-pretreated MSCs.Conclusions Salidroside pretreatment on MSCs could improve their survival and migration potentials,subsequently promoting wound healing process under hyperglycemia.This prospective MSC-based therapy could serve as a novel strategy to improve diabetic wound healing.展开更多
This study investigated the effects of progesterone(P4) on the production and survival of neurons in the hippocampal dentate gyrus of adult male mice.The administration of P4(4 mg/kg) for 3 consecutive days beginning ...This study investigated the effects of progesterone(P4) on the production and survival of neurons in the hippocampal dentate gyrus of adult male mice.The administration of P4(4 mg/kg) for 3 consecutive days beginning on the 0-2 nd day after the first BrdU-injection(BrdU-D0-2) produced an approximately twofold increase in the number of 28-and 56-day-old BrdU(+) cells in comparison to the controls,whereas it did not alter the number of 24 /48-h-old BrdU(+) cells.P4 preferentially promoted the survival of newborn neurons when administered at BrdU-D5-7,but not at BrdU-D10-12 and BrdU-D15-17.Androstenedione(Ad),testosterone(TE),or estradiol(E2) at the same-dose of P4,when administered at BrdU-D0-2,could not replicate the effect of P4,while the inhibition of 5 alpha-reductase by finasteride did not affect the P4-action,indicating that the P4-effect is exerted by P4 itself but not by its metabolites.On the other hand,the P4R antagonist RU486 partially suppressed the P4-effect,while inhibitors for Src,MEK,or PI3K totally suppressed the P4-effect.Finally,the P4-enhanced survival of newborn neurons was accompanied by a potentiation of spatial learning and memory,which was P4R-dependent.These findings suggest that P4 enhances the survival of newborn neurons through P4R and /or the Src-ERK and PI3K pathways independent of its influence on cell proliferation,which is well correlated with the potentiated spatial cognitive function of P4-treated animals.展开更多
Metastasis is the main cause of cancer death,and tumor cells mainly disseminate to the distal organs through the blood circulation,in which they experience considerable levels of fluid shear stress.CTCs are heterogene...Metastasis is the main cause of cancer death,and tumor cells mainly disseminate to the distal organs through the blood circulation,in which they experience considerable levels of fluid shear stress.CTCs are heterogeneous with diverse subpopulations of distinct genotypes and phenotypes and the frequency of CTCs is correlated with poor prognosis and overall survival in cancer patients.Less than 0.01%of them may eventually generate metastatic tumors in secondary sites,indicating the inefficiency of metastasis.Nevertheless,metastasis accounts for over 90%of cancer-related deaths,suggesting that a subpopulation of CTCs are able to survive the metastatic process and form metastases.To target metastasis,it is thus essential to understand the roles of various factors during dissemination in the survival and functions of CTCs.However,the effects of hemodynamic shear stress on biophysical properties and functions of CTCs in suspension are not fully understood.This study was to investigate the effect of hemodynamic shear stress on the survival and anti-chemotherapy ability of suspended circulating tumor cells during metastasis,and the effect of actomyosin activity on this regulation.In this study,we developed a circulatory system to generate physiologic levels of hemodynamic shear stress,which mimicked certain important aspects of the CTC microenvironment in blood circulation.The survival of tumor cells in suspension,as a model for real CTCs,under different shear stress and circulation duration was examined.We found that the majority of breast tumor cells s in suspension can be eliminated by hemodynamic shear stress.The surviving cells exhibit unique biophysical properties,including significantly retarded cell adhesion,mesenchymal-like cell morphology,and reduced F-actin expression and cellular stiffness.Cancer stem cells which has been reported in other papers have lower stiffness compared with conventional tumor cells showed significantly higher survival in blood flow.Importantly,low actomyosin activity promotes the survival of CTCs in blood shear flow while high actomyosin activity inhibits tumor cells surviving shear stress treatment.These findings might be explained by the up-and down-regulation of the anti-apoptosis genes.Soft surviving tumor cells held survival advantages in shear flow and higher resistance to chemotherapy.Metastasis is closely linked with chemoresistance.However,the underlying mechanisms have not been fully understood,in particular,the roles of hemodynamic shear stress and actomyosin-dependent cell mechanics in drug resistance of CTCs remain unclear.Inhibiting actomyosin activity in suspended tumor cells enhanced chemoresistance,while activating actomyosin suppressed this ability.These findings might be associated with the corresponding changes in multidrug resistance related genes.Our study unveils the regulatory roles of actomyosin in the survival and drug resistance of circulating tumor cells in hemodynamic shear flow,which imply the importance of fluid shear stress and actomyosin activity in tumor metastasis.Our findings reveal a new mechanism by which circulating tumor cells are able to survive hemodynamic shear stress and chemotherapy and may offer a new potential strategy to target circulating tumor cells in shear flow and combat chemoresistance through actomyosin.展开更多
Background and objective Non-small cell lung cancer (NSCLC) stages over IIIb still remain as an intractable disease.Survival rate of NSCLC stages over IIIb could be increased through chemotherapy and radiation,but res...Background and objective Non-small cell lung cancer (NSCLC) stages over IIIb still remain as an intractable disease.Survival rate of NSCLC stages over IIIb could be increased through chemotherapy and radiation,but results are not satisfactory.Oriental medicine herbal formula,HangAm-Dan (HAD) has been developed for anti-tumor purpose and several previous studies have already reported its effects.The aim of this study is to assess HAD's efficacy on prolonging the survival rate of NSCLC stages over IIIb.Methods We have administered 3 000 mg of HAD daily to patients.The study included 74 first visit patients of East-West Cancer Center (EWCC) from November 2007 to April 2008,diagnosed with inoperable NSCLC stages over IIIb.Among them,30 patients were in HAD group and 44 patients were in combined group with conventional therapy and HAD.We have observed and analyzed their overall survival.Results Of total 74 patients,overall 1 year,2 year survival rates and the median survival time were 62.1%,34.9% and 17.0 months (95%CI: 12.9-21.1).NSCLC stage IIIb patients showed higher survival rates than NSCLC stage IV patients (P=0.408).The 1 year,2 year survival rates and the median survival time of the combined group were 70.5%,37.9% and 20.0 months (95%CI: 16.4-24.6).In HAD group,the 1 year,2 year survival rates and the median survival time were 50.0%,25.7% and 12.0 months (95%CI: 6.6-17.4).The combined therapy group showed higher survival rates than the HAD group (P=0.034).Each groups treated with HAD for more than 4 weeks showed higher survival rates than those treated for less than 4 weeks,but there was no significant difference (P=0.278).In hazard ratio,the combined therapy group showed lower mortality rate than the HAD group with statistical significance (P=0.040).Conclusion HAD could prolong the survival rate of inoperable NSCLC stages over IIIb.HAD is more effective when combined with conventional therapy.In the future,more controlled clinical trials with larger sample in multi-centers are needed to reevaluate the efficacy and safety of HAD.Keywords Lung neoplasms; HangAm-Dan; Oriental medicine; Overall survival rate; Cancer; Herb Abstract Background and objective Non-small cell lung cancer (NSCLC) stages over IIIb still remain as an intractable disease.Survival rate of NSCLC stages over IIIb could be increased through chemotherapy and radiation,but results are not satisfactory.Oriental medicine herbal formula,HangAm-Dan (HAD) has been developed for anti-tumor purpose and several previous studies have already reported its effects.The aim of this study is to assess HAD's efficacy on prolonging the survival rate of NSCLC stages over IIIb.Methods We have administered 3 000 mg of HAD daily to patients.The study included 74 first visit patients of East-West Cancer Center (EWCC) from November 2007 to April 2008,diagnosed with inoperable NSCLC stages over IIIb.Among them,30 patients were in HAD group and 44 patients were in combined group with conventional therapy and HAD.We have observed and analyzed their overall survival.Results Of total 74 patients,overall 1 year,2 year survival rates and the median survival time were 62.1%,34.9% and 17.0 months (95%CI: 12.9-21.1).NSCLC stage IIIb patients showed higher survival rates than NSCLC stage IV patients (P=0.408).The 1 year,2 year survival rates and the median survival time of the combined group were 70.5%,37.9% and 20.0 months (95%CI: 16.4-24.6).In HAD group,the 1 year,2 year survival rates and the median survival time were 50.0%,25.7% and 12.0 months (95%CI: 6.6-17.4).The combined therapy group showed higher survival rates than the HAD group (P=0.034).Each groups treated with HAD for more than 4 weeks showed higher survival rates than those treated for less than 4 weeks,but there was no significant difference (P=0.278).In hazard ratio,the combined therapy group showed lower mortality rate than the HAD group with statistical significance (P=0.040).Conclusion HAD could prolong the survival rate of inoperable NSCLC stages over IIIb.HAD is more effective when combined with conventional therapy.In the future,more controlled clinical trials with larger sample in multi-centers are needed to reevaluate the efficacy and safety of HAD.展开更多
The problem of "life and death" has been a confusing proposition of philosophy since long ago,for which philosophers both at home and abroad take great pains to pursue the answer.The problem of"life and...The problem of "life and death" has been a confusing proposition of philosophy since long ago,for which philosophers both at home and abroad take great pains to pursue the answer.The problem of"life and death"is also attractive for litterateurs.This paper attempts to scrutinize the works of Franz Kafka and based on comments of different critics,simply analyzing the theory of survival and the theory of death and exploring the aesthetic value.Through analysis,the author of this paper concludes that the theory of survival in the works of Kafka tends to express hating of not being favored by chances and the fright and anxiety of the time;on the contrary,the theory of death in his works tends to express worship and belief.Both life and death are expressed vividly in his works,showing the brave pursuit of senior artistic forms of Kafka and the essence of its aesthetic value.展开更多
Objective:During the past decades,the incidence of colorectal cancer was increased all around the world.In Egypt,colorectal cancer is the 7th most common cancer.The purpose of this study is to study the problem of col...Objective:During the past decades,the incidence of colorectal cancer was increased all around the world.In Egypt,colorectal cancer is the 7th most common cancer.The purpose of this study is to study the problem of colorectal cancer in Alexandria:trend,and survival.Methods:Two methodological strategies were adopted:Record reviewing for estimation of the annual incidence rates of colorectal cancer,and a retrospective cohort study to calculate the 5-year survival rates of colorectal cancer.Results:The annual incidence rates of CRC in Alexandria in 2007-2008 were 6.33 and 6.45 respectively per 100000 mid-year Alexandria population.The overall 5-years cumulative survival rate for CRC cases was 28.0%.Conclusion:This increase in incidence and mortality rates points toward a failed early detection and prevention strategy as well as failure to address lifestyle and dietary challenges of urbanization that affect most of the globe including Egypt.展开更多
Survivability is used to evaluate the ability of the satellite to complete the mission after failure,while the duration of maintaining performance is often ignored.An effective backup strategy can restore the constell...Survivability is used to evaluate the ability of the satellite to complete the mission after failure,while the duration of maintaining performance is often ignored.An effective backup strategy can restore the constellation performance timely,and maintain good network communication performance in case of satellite failure.From the perspective of network utility,the low Earth orbit(LEO)satellite constellation survivable graphical eva-luation and review technology(GERT)network with backup satel-lites is constructed.A network utility transfer function algorithm based on moment generating function and Mason formula is proposed,the network survivability evaluation models of on-orbit backup strategy and ground backup strategy are established.The survivable GERT model can deduce the expected mainte-nance time of LEO satellite constellation under different fault states and the network utility generated during the state mainte-nance period.The case analysis shows that the proposed surviv-able GERT model can consider the satellite failure rate,backup satellite replacement rate,maneuver control replacement ability and life requirement,and effectively determine the optimal sur-vivable backup strategy for LEO satellite constellation with limi-ted resources according to the expected network utility.展开更多
基金Outstanding Youth Foundation of Hunan Provincial Department of Education(Grant No.22B0911)。
文摘In this paper,we introduce the censored composite conditional quantile coefficient(cC-CQC)to rank the relative importance of each predictor in high-dimensional censored regression.The cCCQC takes advantage of all useful information across quantiles and can detect nonlinear effects including interactions and heterogeneity,effectively.Furthermore,the proposed screening method based on cCCQC is robust to the existence of outliers and enjoys the sure screening property.Simulation results demonstrate that the proposed method performs competitively on survival datasets of high-dimensional predictors,particularly when the variables are highly correlated.
基金supported by the National Natural Science Foundation of China(81572870)
文摘Objective:To explore the relationship between cancer awareness and the survival of the patients with non-small cell lung carcinoma(NSCLC).Methods:A total of 865 NSCLC patients were screened for the risk factors,including age,gender,address,tumor/lymph nodes/metastasis(TNM)stage,and cancer awareness.Survival of the patients was calculated by Kaplan-Meier method and Cox regression analysis.Results:After an average observation time of 304 d(ranging from 0 to 4718 d),62 of the 394 patients in the cancer awareness group survived,whereas 26 of the 471 patients in the cancer concealment group survived.Cancer-specific and all-cause survival was poorer in the cancer concealment group(P<0.001 for each,log-rank test).Cox multivariate regression analysis showed that cancer concealment displayed significantly lower cancer-specific survival[hazard ratio(HR)=1.534,95%con fi dence interval(CI)1.320 to 1.784,P<0.001]and all-cause survival(HR=1.558,95%CI 1.346 to 1.803,P<0.001).Conclusion:Cancer concealment is associated with a poor survival of NSCLC patients,which may prohibit the patients from obtaining the real“right to survival”.
基金Supported by National Agricultural Translation Fund (02EFN212301073)
文摘Probiotics which can provide potential health benefits for consumers and prevent disease, is the most important research field for functional food in the future. It is the key point that how much the count of bacteria and how long it can preserve. Freeze-drying skill is one of the best preservation methods, but it＇s defect that damage to biological systems can be attributed to changes in the physical state of membrane lipids or/and changes in the structure of sensitive proteins and the decreased survival rate. This work used pretreatment methods-cold shock and hot shock to reduce the damage to bacteria during freeze-drying. Using unpretreated samples as control, aspects of cold shock or heat shock. The response of Enterococcous faecalis A31 was investigated during lag phase, the middle of exponential growth phase and the terminal of exponential growth phase. The results suggested that when cold shock, the shock protein concentration produced by treated sample within 2 h during the middle of exponential growth phase was higher than 4, 8, 24 h, The concentration of shock protein produced by treated sample at 10 ℃ was higher than 20℃, The concentration of sample protein at the middle of exponential growth phase was higher than that at the terminal of exponential growth phase. After one-month storage, the survival rate at 10℃ was better than 20 ℃ and 4 ℃comparatively. The survival rate at （6 h） 4 ℃/24 h （lag period） was higher than （10 h） 4 ℃/24 h （the middle of exponential growth phase）, and the effect of 10℃/8 h shock treatments was best during the middle of exponential growth phase, when hot shock, The concentration of heat shock proteins produced was not obvious, and survival rate was higher at 45 ℃, 30 min than at 45 ℃, 60 min.
基金Project(CYB14010)supported by Chongqing Graduate Student Research Innovation Project,ChinaProject(51405209)supported by the National Natural Science Foundation of China
文摘Heliostats are sensitive to the wind load, thus as a key indicator, the study on the static and dynamic stability bearing capacity for heliostats is very important. In this work, a numerical wind tunnel was established to calculate the wind load coefficients in various survival stow positions. In order to explore the best survival stow position for the heliostat under the strong wind, eigenvalue buckling analysis method was introduced to predict the critical wind load theoretically. Considering the impact of the nonlinearity and initial geometrical imperfection, the nonlinear post-buckling behaviors of the heliostat were investigated by load-displacement curves in the full equilibrium process. Eventually, combining B-R criterion with equivalent displacement principle the dynamic critical wind speed and load amplitude coefficient were evaluated. The results show that the determination for the best survival stow position is too hasty just by the wind load coefficients. The geometric nonlinearity has a great effect on the stability bearing capacity of the heliostat, while the effects of the material nonlinearity and initial geometrical imperfection are relatively small. And the heliostat is insensitive to the initial geometrical imperfection. In addition, the heliostat has the highest safety factor for wind-resistant performance in the stow position of 90-90 which can be taken as the best survival stow position. In this case, the extreme survival wind speeds for the static and dynamic stability are 150 m/s and 36 m/s, respectively.
基金Supported by grants from the National Natural Science Foundation of China ( 81372202,81872273, 31871367)
文摘Objective Diabetic patients pose a greater challenge in managing chronic wound healing,leading to a higher amputation risk compared to non-diabetic patients.Due to their paracrine function by secreting various cytokines and angiogenic factors,mesenchymal stem cells(MSCs)have been acknowledged to be a potential agent in modulating wound healing process.However,post-transplanted MSCs are vulnerable to death,indicating poor survival and migration ability in the wound site of the host,especially under hyperglycemia.As hyperglycemia induces reactive oxygen species(ROS)generation and cellular apoptosis,improvement of MSCs survival and migration potentials under hyperglycemia could contribute to a more efficient MSCs-based wound healing therapy.Salidroside(Sa),a small-molecule drug derived from Rhodiola plant,has been proved to enhance the paracrine function of skeletal muscle cells,as well as their migration even under hypoxichyperglycemia.Herein,we investigated whether Sa could improve the survival and migration potentials of MSCs,subsequently enhance the wound healing process under hyperglycemia.Methods MSCs were cultured under three conditions:low glucose,high glucose,and high glucose+Sa.qPCR analysis and western blotting were done to examine the mRNA and protein expression level of several factors which are important in upregulating the wound healing process.MTT colorimetric assay,intracellular ROS detection,and flow cytometry assay were employed to examine the effect of Sa in MSCs survival.Transwell chamber assay,scratch assay,and phalloidin staining were done to elucidate the role of Sa in regulating MSCs migration potential.For in vivo experiment,diabetic wound healing mice model was generated to elucidate the effect of Sa-pretreated MSCs transplantation in wound closure rate,as well as re-epithelization status,observed with hematoxylin and eosin staining.The diabetic wound healing mice model were divided into three groups:1)mice injected with PBS,2)mice transplanted with PBS-pretreated MSCs,and 3)mice transplanted with Sa-pretreated MSCs.Results(1)Hyperglycemic condition induced the generation of ROS and suppressed total cell number of MSCs,while Sa treatment into MSCs restored these hyperglycemia-induced alterations.In line with this,total apoptotic cells were also suppressed by treating MSCs with Sa.The expression level of cell survival factor,heme-oxygenase 1(HO-1),was enhanced in Sa-pretreated MSCs.Further treatment of HO-1 inhibitor into Sa-pretreated MSCs nullified the ROS level and total apoptotic cells,indica-ting the importance of HO-1 in mediating the Sa-induced survival of MSCs under hyperglycemia.(2)Transwell chamber and scratch assay results showed that Sa-pretreated MSCs have a higher migration potential under hyperglycemia,supported by higher F-actin polymerization fractal dimension.Fibroblast growth factor 2(FGF2)and hepatocyte growth factor(HGF)expression level,which are essential factors for cell migration,were also improved in Sa-pretreated MSCs under hyperglycemia.(3)In diabetic wound healing mice model,transplantation of Sa-pretreated MSCs resulted in significantly improved wound closure rate and re-epithelization.The protein levels of HO-1,FGF2,and HGF were also enhanced in the tissues obtained from the wound site of diabetic wound healing mice model which were transplanted with Sa-pretreated MSCs.Conclusions Salidroside pretreatment on MSCs could improve their survival and migration potentials,subsequently promoting wound healing process under hyperglycemia.This prospective MSC-based therapy could serve as a novel strategy to improve diabetic wound healing.
文摘This study investigated the effects of progesterone(P4) on the production and survival of neurons in the hippocampal dentate gyrus of adult male mice.The administration of P4(4 mg/kg) for 3 consecutive days beginning on the 0-2 nd day after the first BrdU-injection(BrdU-D0-2) produced an approximately twofold increase in the number of 28-and 56-day-old BrdU(+) cells in comparison to the controls,whereas it did not alter the number of 24 /48-h-old BrdU(+) cells.P4 preferentially promoted the survival of newborn neurons when administered at BrdU-D5-7,but not at BrdU-D10-12 and BrdU-D15-17.Androstenedione(Ad),testosterone(TE),or estradiol(E2) at the same-dose of P4,when administered at BrdU-D0-2,could not replicate the effect of P4,while the inhibition of 5 alpha-reductase by finasteride did not affect the P4-action,indicating that the P4-effect is exerted by P4 itself but not by its metabolites.On the other hand,the P4R antagonist RU486 partially suppressed the P4-effect,while inhibitors for Src,MEK,or PI3K totally suppressed the P4-effect.Finally,the P4-enhanced survival of newborn neurons was accompanied by a potentiation of spatial learning and memory,which was P4R-dependent.These findings suggest that P4 enhances the survival of newborn neurons through P4R and /or the Src-ERK and PI3K pathways independent of its influence on cell proliferation,which is well correlated with the potentiated spatial cognitive function of P4-treated animals.
基金the support from National Natural Science Foundation of China ( 11672255)Shenzhen Science and Technology Innovation Commission ( JCYJ20170303160515987, JCYJ20170413154735522 )+1 种基金Early Career Scheme from Research Grants Council of the Hong Kong Special Administrative Region,China ( PolyU 252094 /17E)the internal grant from the Hong Kong Polytechnic University ( 1-ZE4Q,1-ZVJ8)
文摘Metastasis is the main cause of cancer death,and tumor cells mainly disseminate to the distal organs through the blood circulation,in which they experience considerable levels of fluid shear stress.CTCs are heterogeneous with diverse subpopulations of distinct genotypes and phenotypes and the frequency of CTCs is correlated with poor prognosis and overall survival in cancer patients.Less than 0.01%of them may eventually generate metastatic tumors in secondary sites,indicating the inefficiency of metastasis.Nevertheless,metastasis accounts for over 90%of cancer-related deaths,suggesting that a subpopulation of CTCs are able to survive the metastatic process and form metastases.To target metastasis,it is thus essential to understand the roles of various factors during dissemination in the survival and functions of CTCs.However,the effects of hemodynamic shear stress on biophysical properties and functions of CTCs in suspension are not fully understood.This study was to investigate the effect of hemodynamic shear stress on the survival and anti-chemotherapy ability of suspended circulating tumor cells during metastasis,and the effect of actomyosin activity on this regulation.In this study,we developed a circulatory system to generate physiologic levels of hemodynamic shear stress,which mimicked certain important aspects of the CTC microenvironment in blood circulation.The survival of tumor cells in suspension,as a model for real CTCs,under different shear stress and circulation duration was examined.We found that the majority of breast tumor cells s in suspension can be eliminated by hemodynamic shear stress.The surviving cells exhibit unique biophysical properties,including significantly retarded cell adhesion,mesenchymal-like cell morphology,and reduced F-actin expression and cellular stiffness.Cancer stem cells which has been reported in other papers have lower stiffness compared with conventional tumor cells showed significantly higher survival in blood flow.Importantly,low actomyosin activity promotes the survival of CTCs in blood shear flow while high actomyosin activity inhibits tumor cells surviving shear stress treatment.These findings might be explained by the up-and down-regulation of the anti-apoptosis genes.Soft surviving tumor cells held survival advantages in shear flow and higher resistance to chemotherapy.Metastasis is closely linked with chemoresistance.However,the underlying mechanisms have not been fully understood,in particular,the roles of hemodynamic shear stress and actomyosin-dependent cell mechanics in drug resistance of CTCs remain unclear.Inhibiting actomyosin activity in suspended tumor cells enhanced chemoresistance,while activating actomyosin suppressed this ability.These findings might be associated with the corresponding changes in multidrug resistance related genes.Our study unveils the regulatory roles of actomyosin in the survival and drug resistance of circulating tumor cells in hemodynamic shear flow,which imply the importance of fluid shear stress and actomyosin activity in tumor metastasis.Our findings reveal a new mechanism by which circulating tumor cells are able to survive hemodynamic shear stress and chemotherapy and may offer a new potential strategy to target circulating tumor cells in shear flow and combat chemoresistance through actomyosin.
文摘Background and objective Non-small cell lung cancer (NSCLC) stages over IIIb still remain as an intractable disease.Survival rate of NSCLC stages over IIIb could be increased through chemotherapy and radiation,but results are not satisfactory.Oriental medicine herbal formula,HangAm-Dan (HAD) has been developed for anti-tumor purpose and several previous studies have already reported its effects.The aim of this study is to assess HAD's efficacy on prolonging the survival rate of NSCLC stages over IIIb.Methods We have administered 3 000 mg of HAD daily to patients.The study included 74 first visit patients of East-West Cancer Center (EWCC) from November 2007 to April 2008,diagnosed with inoperable NSCLC stages over IIIb.Among them,30 patients were in HAD group and 44 patients were in combined group with conventional therapy and HAD.We have observed and analyzed their overall survival.Results Of total 74 patients,overall 1 year,2 year survival rates and the median survival time were 62.1%,34.9% and 17.0 months (95%CI: 12.9-21.1).NSCLC stage IIIb patients showed higher survival rates than NSCLC stage IV patients (P=0.408).The 1 year,2 year survival rates and the median survival time of the combined group were 70.5%,37.9% and 20.0 months (95%CI: 16.4-24.6).In HAD group,the 1 year,2 year survival rates and the median survival time were 50.0%,25.7% and 12.0 months (95%CI: 6.6-17.4).The combined therapy group showed higher survival rates than the HAD group (P=0.034).Each groups treated with HAD for more than 4 weeks showed higher survival rates than those treated for less than 4 weeks,but there was no significant difference (P=0.278).In hazard ratio,the combined therapy group showed lower mortality rate than the HAD group with statistical significance (P=0.040).Conclusion HAD could prolong the survival rate of inoperable NSCLC stages over IIIb.HAD is more effective when combined with conventional therapy.In the future,more controlled clinical trials with larger sample in multi-centers are needed to reevaluate the efficacy and safety of HAD.Keywords Lung neoplasms; HangAm-Dan; Oriental medicine; Overall survival rate; Cancer; Herb Abstract Background and objective Non-small cell lung cancer (NSCLC) stages over IIIb still remain as an intractable disease.Survival rate of NSCLC stages over IIIb could be increased through chemotherapy and radiation,but results are not satisfactory.Oriental medicine herbal formula,HangAm-Dan (HAD) has been developed for anti-tumor purpose and several previous studies have already reported its effects.The aim of this study is to assess HAD's efficacy on prolonging the survival rate of NSCLC stages over IIIb.Methods We have administered 3 000 mg of HAD daily to patients.The study included 74 first visit patients of East-West Cancer Center (EWCC) from November 2007 to April 2008,diagnosed with inoperable NSCLC stages over IIIb.Among them,30 patients were in HAD group and 44 patients were in combined group with conventional therapy and HAD.We have observed and analyzed their overall survival.Results Of total 74 patients,overall 1 year,2 year survival rates and the median survival time were 62.1%,34.9% and 17.0 months (95%CI: 12.9-21.1).NSCLC stage IIIb patients showed higher survival rates than NSCLC stage IV patients (P=0.408).The 1 year,2 year survival rates and the median survival time of the combined group were 70.5%,37.9% and 20.0 months (95%CI: 16.4-24.6).In HAD group,the 1 year,2 year survival rates and the median survival time were 50.0%,25.7% and 12.0 months (95%CI: 6.6-17.4).The combined therapy group showed higher survival rates than the HAD group (P=0.034).Each groups treated with HAD for more than 4 weeks showed higher survival rates than those treated for less than 4 weeks,but there was no significant difference (P=0.278).In hazard ratio,the combined therapy group showed lower mortality rate than the HAD group with statistical significance (P=0.040).Conclusion HAD could prolong the survival rate of inoperable NSCLC stages over IIIb.HAD is more effective when combined with conventional therapy.In the future,more controlled clinical trials with larger sample in multi-centers are needed to reevaluate the efficacy and safety of HAD.
文摘The problem of "life and death" has been a confusing proposition of philosophy since long ago,for which philosophers both at home and abroad take great pains to pursue the answer.The problem of"life and death"is also attractive for litterateurs.This paper attempts to scrutinize the works of Franz Kafka and based on comments of different critics,simply analyzing the theory of survival and the theory of death and exploring the aesthetic value.Through analysis,the author of this paper concludes that the theory of survival in the works of Kafka tends to express hating of not being favored by chances and the fright and anxiety of the time;on the contrary,the theory of death in his works tends to express worship and belief.Both life and death are expressed vividly in his works,showing the brave pursuit of senior artistic forms of Kafka and the essence of its aesthetic value.
文摘Objective:During the past decades,the incidence of colorectal cancer was increased all around the world.In Egypt,colorectal cancer is the 7th most common cancer.The purpose of this study is to study the problem of colorectal cancer in Alexandria:trend,and survival.Methods:Two methodological strategies were adopted:Record reviewing for estimation of the annual incidence rates of colorectal cancer,and a retrospective cohort study to calculate the 5-year survival rates of colorectal cancer.Results:The annual incidence rates of CRC in Alexandria in 2007-2008 were 6.33 and 6.45 respectively per 100000 mid-year Alexandria population.The overall 5-years cumulative survival rate for CRC cases was 28.0%.Conclusion:This increase in incidence and mortality rates points toward a failed early detection and prevention strategy as well as failure to address lifestyle and dietary challenges of urbanization that affect most of the globe including Egypt.
基金This work was supported by the National Natural Science Foundation of China(72271124,52232014,72071111,71801127,71671091).
文摘Survivability is used to evaluate the ability of the satellite to complete the mission after failure,while the duration of maintaining performance is often ignored.An effective backup strategy can restore the constellation performance timely,and maintain good network communication performance in case of satellite failure.From the perspective of network utility,the low Earth orbit(LEO)satellite constellation survivable graphical eva-luation and review technology(GERT)network with backup satel-lites is constructed.A network utility transfer function algorithm based on moment generating function and Mason formula is proposed,the network survivability evaluation models of on-orbit backup strategy and ground backup strategy are established.The survivable GERT model can deduce the expected mainte-nance time of LEO satellite constellation under different fault states and the network utility generated during the state mainte-nance period.The case analysis shows that the proposed surviv-able GERT model can consider the satellite failure rate,backup satellite replacement rate,maneuver control replacement ability and life requirement,and effectively determine the optimal sur-vivable backup strategy for LEO satellite constellation with limi-ted resources according to the expected network utility.
